The proposed Superfund Basic Research Center at Boston University consists of a program of research and interdisciplinary training organized around nine closely connected research projects that investigate the effects of specific toxic exposures in the community setting and the underlying mechanisms of action of these exposures; and the detection and mechanism of effects in human and non-human populations exposed to complex mixtures near a Superfund site. In addition there will be an outreach component to bring the results of the research to the affected community and to encourage the interest and engagement of young investigators and investigators-to-be. Three epidemiology projects study etiologic factors in breast cancer. Project 1 is a population-based case-control study of breast cancer risk and exposure to tetrachloroethylene (PCE) in drinking water on the Upper Cape. Project 2 applies new methods and technologies for environmental epidemiology, specifically, several new methods to detect and verify spatial aggregation ("hot spots" or cluster). Project 3 is a nested case- control study within three cohorts of Danish women who had serum samples taken between 1976 and 1982. Approximately 215 of these women have since gone on to develop breast cancer. Comparison between cases and controls will be made for DDE and specific PCB congener. Four projects will carry out detailed mechanistic studies on topic related to the epidemiological studies. Projects 4-6 examine mechanisms by which certain classes of xenobiotics induce transcription of specific genes encoding the cytochrome P450 mixed function oxidases, enzymes important in the metabolism of a range of compounds, including PVBs, DDE and PCE. Project 7 explores effects on male reproductive biology of xenobiotics using a unique in vitro model of spermatogenesis. Two projects examine the influence of contaminated groundwater on surface waters. The site of both projects is the area studied in projects 1 and 2 and involve ponds where previous epidemiologic data suggests an increased risk of cancer among those who reported swimming there. Project 8 will study how a contaminated groundwater plume from the MMR Superfund site interacts with surface water, where there is exposure of humans and aquatic species. Project 9 will examine the effects of pollution of the ponds on reproductive biology in teleost fish, frogs and turtles.